This proposal describes a study to determine the relation of retinal microvascular signs to incident cardiovascular disease (stroke and coronary heart disease [CHD]), prevalent cognitive impairment, prevent depression and apoliprotein E (APOE) gene in older persons participating in the Cardiovascular Health Study (CHS). It builds upon new data that in middle-aged people, retinal microvascular signs, as documented from retinal photographs, are associated with a range of cardiovascular disorders, including stroke, CHD (in women) and cognitive dysfunction, independent of blood pressure and other risk factors. The CHS is a population-based study of four communities among older people where both retinal microvascular changes and systemic vascular diseases are measured in detail according to standard protocols. Participants were first examined at baseline in 1989-90, and followed up yearly. In 1997-98, retinal photography was added to the study examination, when participants had a median age of 77 years (range 69 to 97 years). These photographs have already been graded for presence of retinal microvascular signs (retinopathy, generalized and focal arteriolar narrowing, and arterio-venous nicking) according to a standardized protocol. At each examination, detailed information was collected on cardiovascular disease, cognitive function and depression. APOE genotyping is available on all participants. In the current study, we will examine the relation of retinal vascular signs to incidence of stroke/CHD, prevalence of cognitive impairment and depression, and to the APOE gene. Results of the proposed series of analyses will provide new information regarding the impact of microvascular disease to the development of common vascular conditions of the heart and brain as people age. This may ultimately lead to improved identification, and preventive and therapeutic strategies for the most common causes of morbidity, disability and mortality affecting elderly people in the United States.